1. Field of the Invention
The present invention relates to a solid dosage form, comprising at least one film, which contains an active substance at least in sections. The invention further relates to a method for the production of a solid dosage form with an active substance.
2. Description of Related Art
There are known solid dosage forms containing an active substance, in particular pharmaceutical tablets, in which the active substance is embedded in a matrix of water-soluble, water-swellable or water-dispersible mixtures of substances. Such pharmaceutical dosage forms are also called matrix dosage forms. In such matrix dosage forms the active substance can on the one hand be released by erosion. In this case the dosage form dissolves layer by layer in an aqueous medium, thereby releasing the active substance. There is therefore a direct correlation between the decrease in weight of the dosage form and release of the active substance. On the other hand the active substance can be released by diffusion. By using polymers that are swellable in water, a layer of gel is formed on the surface of the dosage form in the matrix in contact with the aqueous medium, so that the active substance is released via this layer of gel under control by diffusion. In this case there is no direct correlation between any weight change of the dosage form and release of the active substance.
In many applications it is desirable to release the active substance in a precisely defined amount in unit time, especially in equal amount in unit time, over the duration of release of the active substance. In the case when the tablet dissolves, such a release profile can only be achieved with great difficulty, as the tablet surface changes as a function of time. Also in the case of diffusion-controlled release of the active substance, it is not possible to achieve defined release profiles with known solid dosage forms.
In addition to the dosage forms that are to be taken orally, depot dosage forms are also known, which are implanted under the skin. Such implants are used for example for hormone therapy. In most cases they comprise a polymer matrix, in which the active substance is embedded. As the polymers are biodegradable, slow erosion of the implant takes place in the body, and the active substance is slowly released. With these systems, however, there is the problem that initially there is very rapid release of the active substance located in the surfaces of the dosage form. Therefore early after implantation, release of the active substance is very high, which in many cases is a disadvantage. The initially rapid release of the active substance in dosage forms is also termed the “initial burst effect”. The initial burst effect can lead to very excessive levels of the active substance immediately after implantation of a depot dosage form, which is often associated with undesirable side-effects. It is therefore desirable to produce dosage forms with which such an initial burst effect can be avoided.
Solid pharmaceutical dosage forms are produced for example by extrusion of polymer melts containing the pharmaceutical active substance. The extrudate can be shaped to the desired dosage form by calendering. Furthermore, the ground extrudate can be compacted in a tablet press, adding tableting aids if required. A method of production of pharmaceutical tablets is described for example in EP 0 358 107 A2.
A laminar dosage form and a method for its production are known from EP 0 872 234 B1. The dosage form comprises rolled or folded layers of a polymer film that contains a pharmaceutical active substance. The laminar structure of this dosage form means that diffusion of the active substance can essentially only take place at the cut edges and in the layers and out of them, so that the diffusion path is prolonged. In this way a delayed, controlled release of the active substance is achieved.
Furthermore, a solid dosage form in which a layered film is rolled up is known from U.S. Pat. No. 3,625,214. The active substance is distributed homogeneously in a matrix which is applied to a carrier film. The rate of release of the active substance can be controlled by varying the layer thickness or with an additional coating.
Finally, a pharmaceutical preparation suitable for transdermal application in the form of a film is known from DE 29 20 500 A1. The film comprises a copolymer that is compatible with the skin and is swellable in water, in which the drug is embedded in amorphous form with a defined profile. The time-dependent decrease in rate of release owing to the increase in thickness of the diffusion layer over time is compensated in the dosage form by a concentration profile of the active substance which rises in the polymer film with increasing distance from the release surface, so as to keep the rate of release of the active substance almost constant.